Nückel Holger, Frey Ulrich H, Dürig Jan, Dührsen Ulrich, Siffert Winfried
Department of Hematology, Medical Faculty, University of Essen, Essen, Germany.
Eur J Haematol. 2004 Apr;72(4):259-63. doi: 10.1111/j.0902-4441.2003.00210.x.
Purinergic P2X7 receptors are ligand-gated cation channels expressed on the cells of the immune and hemopoietic system which have been shown to mediate the ATP-induced apoptotic death of monocytes, macrophages and lymphocytes. A common single nucleotide polymorphism within the P2X7 gene has been described in exon 13 (1513A/C), the gene products encoding fully active and non-functional proteins. We genotyped the P2X7 1513A/C polymorphism using DNA from 111 patients with chronic lymphocytic leukemia (CLL) and 97 healthy controls using polymerase chain reaction (PCR) amplification followed by Hha1 restriction analysis. We found no significant difference in allele frequency between CLL patients and controls. Time periods from diagnosis to initiation of chemotherapy, a surrogate marker for disease progression, were not different in patients displaying the combined 1513A/C and C/C or the 1513A/A genotype (P = 0.97). Similar results were observed in a subgroup analysis of prognostically more favorable CD38-negative and ZAP-70-negative CLL patients. In conclusion, our data do not support a role of the P2X7 genotype as a prognostic marker in B-cell CLL.
嘌呤能P2X7受体是一种配体门控阳离子通道，表达于免疫和造血系统细胞上，已证明其介导ATP诱导的单核细胞、巨噬细胞和淋巴细胞凋亡死亡。P2X7基因第13外显子（1513A/C）存在一种常见的单核苷酸多态性，该基因产物编码完全活性和无功能的蛋白质。我们使用聚合酶链反应（PCR）扩增，随后进行Hha1限制性分析，对111例慢性淋巴细胞白血病（CLL）患者和97例健康对照的DNA进行P2X7 1513A/C多态性基因分型。我们发现CLL患者和对照之间的等位基因频率没有显著差异。从诊断到开始化疗的时间（疾病进展的替代标志物）在表现出1513A/C和C/C组合或1513A/A基因型的患者中没有差异（P = 0.97）。在预后更有利的CD38阴性和ZAP-70阴性CLL患者的亚组分析中也观察到了类似结果。总之，我们的数据不支持P2X7基因型在B细胞CLL中作为预后标志物的作用。
